a study to evaluate the safety and efficacy of mosunetuzumab (btct4465a) in combination with polatuzumab vedotin in b-cell non-hodgkin lymphoma

Conditions: B-cell Non-Hodgkin Lymphoma

Summary: this study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of intravenous (iv) or subcutaneous (sc) mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large b-cell lymphoma (dlbcl), follicular lymphoma (fl), and mantle cell lymphoma (mcl). it will consist of a dose finding portion followed by an expansion phase for second line or later (2l+) participants with relapsed or refractory (r/r) dlbcl and 2l+ r/r fl. in addition, subcutaneous mosunetuzumab in combination with polatuzumab vedotin will be evaluated in participants with at least 2 prior lines of systemic therapy (3l+) for the treatment of r/r mantle cell lymphoma (mcl) and in participants with 2l+ r/r dlbcl.


Eligibility criteria:
key inclusion criteria: * ecog ps of 0, 1, or 2 * histologically confirmed fl, dlbcl, or mcl * must have received at least one prior systemic treatment regimen containing an anti-cd20-directed therapy for dlbcl or fl * for mcl, participants must have received at least two prior systemic treatment regiments, which include 1) anti-cd20-directed therapy, 2) btk inhibitor, and 3) anthracycline or bendamustine * relapsed to prior regimen(s) after having a documented history of response (complete response \[cr\], cr unconfirmed \[cru\], or partial response \[pr\]) of \>/= 6 months in duration from completion of regimen(s); or, refractory to any prior regimen, defined as no response to the prior therapy, or progression within 6 months of completion of the last dose of therapy * measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as \> 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as \> 1.0 cm in its longest dimension * adequate hematologic, renal, and hepatic function key exclusion criteria: * prior treatment with mosunetuzumab or other cd20-directed bispecific antibodies * prior treatment with polatuzumab vedotin * current \> grade 1 peripheral neuropathy * prior use of any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugate (adc) within 4 weeks before first dose of study treatment * treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment * treatment with radiotherapy within 2 weeks prior to the first dose of study treatment * autologous stem-cell transplantation (sct) within 100 days prior to first study treatment administration * prior treatment with chimeric antigen receptor t-cell (car-t) therapy within 30 days before first study treatment administration * prior allogeneic sct * prior solid organ transplantation * known or suspected history of hemophagocytic lymphohistiocytosis (hlh) * patients with history of confirmed progressive multifocal leukoencephalopathy (pml) * current or past history of central nervous system (cns) lymphoma or cns disease * history of autoimmune disease